Table 2.

Univariable and Multivariable Analyses of Main Outcomes by Renal Function

Event by CrCl	n	Events	Univariable		Multivariable
			HR (95% CI)	P Value	HR (95% CI)	P Value	Trend P Value
Stroke/SEEs							0.053
<15 mL/min	404	21 (5.2)	2.35 (1.51-3.66)	<0.001	1.59 (0.99-2.56)	0.053	—
15-<30 mL/min	3,465	137 (4.0)	1.67 (1.36-2.04)	<0.001	1.31 (1.02-1.67)	0.032	—
30-<50 mL/min	10,764	329 (3.1)	1.21 (1.04-1.42)	0.017	1.10 (0.92-1.30)	0.298	—
≥50 mL/min	11,569	299 (2.6)	ref	—	ref	—	—
Major bleeding							0.232
<15 mL/min	404	18 (4.5)	2.93 (1.81-4.75)	<0.001	1.61 (0.96-2.72)	0.074	—
15-<30 mL/min	3,465	96 (2.8)	1.67 (1.32-2.13)	<0.001	1.12 (0.84-1.50)	0.439	—
30-<50 mL/min	10,764	216 (2.0)	1.14 (0.94-1.38)	0.174	0.95 (0.77-1.16)	0.605	—
≥50 mL/min	11,569	208 (1.8)	ref	—	ref	—	—
Intracranial hemorrhage							0.745
<15 mL/min	404	8 (2.0)	1.76 (0.87-3.59)	0.117	0.98 (0.46-2.07)	0.951	—
15-<30 mL/min	3,465	57 (1.7)	1.36 (1.00-1.84)	0.049	0.95 (0.66-1.37)	0.784	—
30-<50 mL/min	10,764	153 (1.4)	1.11 (0.88-1.38)	0.379	0.94 (0.73-1.20)	0.593	—
≥50 mL/min	11,569	152 (1.3)	ref	—	ref	—	—
Major plus clinically relevant nonmajor bleeding							0.002
<15 mL/min	404	32 (7.9)	2.72 (1.90-3.90)	<0.001	1.80 (1.22-2.65)	0.003
15-<30 mL/min	3,465	204 (5.9)	1.86 (1.57-2.20)	<0.001	1.34 (1.09-1.65)	0.005
30-<50 mL/min	10,764	417 (3.9)	1.15 (1.00-1.31)	0.051	0.99 (0.85-1.15)	0.920
≥50 mL/min	11,569	400 (3.5)	ref		ref
All bleeding							0.037
<15 mL/min	404	54 (13.4)	2.21 (1.68-2.91)	<0.001	1.53 (1.14-2.07)	0.005	—
15-<30 mL/min	3,465	347 (10.0)	1.50 (1.33-1.70)	<0.001	1.13 (0.97-1.32)	0.107	—
30-<50 mL/min	10,764	848 (7.9)	1.11 (1.01-1.22)	0.036	0.98 (0.88-1.09)	0.672	—
≥50 mL/min	11,569	842 (7.3)	ref	—	ref	—	—
Gastrointestinal bleeding							0.090
<15 mL/min	404	26 (6.4)	2.32 (1.56-3.45)	<0.001	1.65 (1.07-2.55)	0.023
15-<30 mL/min	3,465	160 (4.6)	1.54 (1.28-1.86)	<0.001	1.14 (0.91-1.43)	0.250
30-<50 mL/min	10,764	391 (3.6)	1.15 (0.99-1.32)	0.060	1.01 (0.87-1.18)	0.859
≥50 mL/min	11,569	375 (3.2)	ref		ref
Cardiovascular death							<0.001
<15 mL/min	404	32 (7.9)	11.54 (7.73-17.22)	<0.001	5.68 (3.63-8.88)	<0.001
15-<30 mL/min	3,465	206 (6.0)	7.96 (6.24-10.15)	<0.001	4.35 (3.25-5.83)	<0.001
30-<50 mL/min	10,764	226 (2.1)	2.62 (2.06-3.33)	<0.001	2.03 (1.57-2.62)	<0.001
≥50 mL/min	11,569	95 (0.8)
All-cause death							<0.001
<15 mL/min	404	113 (28.0)	9.19 (7.46-11.31)	<0.001	4.46 (3.53-5.64)	<0.001	—
15-<30 mL/min	3,465	568 (16.4)	4.96 (4.37-5.63)	<0.001	2.72 (2.33-3.18)	<0.001	—
30-<50 mL/min	10,764	763 (7.1)	2.01(1.78-2.26)	<0.001	1.51 (1.33-1.72)	<0.001	—
≥50 mL/min	11,569	419 (3.6)	ref	—	ref	—	—
Net clinical outcome							<0.001
<15 mL/min	404	131 (32.4)	5.83 (4.85-7.02)	<0.001	3.11 (2.53-3.82)	<0.001	—
15-<30 mL/min	3,465	691 (19.9)	3.28 (2.96-3.63)	<0.001	2.00 (1.77-2.27)	<0.001	—
30-<50 mL/min	10,764	1,112 (10.3)	1.59 (1.45-1.74)	<0.001	1.26 (1.14-1.40)	<0.001	—
≥50 mL/min	11,569	773 (6.7)	ref	—	ref	—	—

Values are n (%), unless otherwise indicated. The CrCl ≥50 subgroup served as the reference.

Sex, age, body mass index, history of major bleeding, atrial fibrillation type, hypertension, severe hepatic dysfunction, diabetes mellitus, hyperuricemia, heart disease (heart failure, left ventricular systolic dysfunction), myocardial infarction, cerebrovascular disease, thrombosis/embolism-related disease, active cancer, dementia, fall within 1 year, anticoagulants, catheter ablation, antiarrhythmics, antiplatelet drugs, proton pump inhibitors, P-glycoprotein inhibitors, dyslipidemia, gastrointestinal disease, and polypharmacy were included in the model.

CrCl = creatinine clearance; SEE = systemic embolic event(s).